Your Digest for Friday, May 24, 2024 10:59 PM


Myeloma -> plasma cell malignancy in bone marrow producing Ig.

Presenting features of multiple myeloma

Presenting signs and symptoms of multiple myeloma (MM) include

Serum protein electrophoresis patterns

(i.e albumin is 1.5 to 2.5 the level of globulin)

MyelomaBoneMarrow.png

  1. Cast nephropathy: Light chains -> freely filtered at glomerulus -> resorbed but resorbtive capacity exceeded in MM -> precipitate in the tubule in combination with Tamm-horsfall proteins-> CAST NEPHROPATHY. Usually presents as Acute or subacute kidney injury.
    1. Light chains appear in urine as Bence Jones proteins.
  2. AL amyloidosis, caused by myeloma light chains, results in glomerular deposition of AL amyloid in the mesangial, subepithelial, or subendothelial areas or a combination. Amyloid deposition is with randomly oriented, nonbranching fibrils composed of the variable regions of lambda light chains.

[!INFO] Renal involvement in myeloma
"Renal failure is the second most common cause of mortality in patients with multiple myeloma, second only to infections"

[!INFO]
pathologyRenalAmyloidosis.png

  1. Pale deposits of amyloid
  2. Amyloid PAS stains
  3. Congo red apple green birefringence
  4. Amyloid fibrils on EM

"Light chain deposition disease", which also can occur with lymphoma and macroglobulinemia, is glomerular deposition of nonpolymerized light chains (ie, without fibrils), generally the constant regions of kappa chains.
"LCDD must be differentiated from AL amyloidosis. LCDD is Congo red negative and is usually IF positive for κ rather than λ light chain.
Moreover, in LCDD the deposits are subendothelial and granular, whereas in amyloidosis they are composed of randomly arranged fibrils."
[!INFO] Kappa Vs. Lamba light chains:
Kappa light chains are coded on chromosome 2.
Lambda light chains are coded on chromosome 22.
"We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly" Source

Heavy chain deposition (?rarer) in different areas of the kidney can cause immunoglobulin-associated amyloidosis. This usually presents with proteinura or nephrotic syndrome.

Treatment of myeloma kidney

Most common clinical manifestations of renal amyloidosis are proteinuria with frequent nephrotic syndrome and progressive renal dysfunction
Replacement or normal bone marrow tissue and alteration of normal marrow environment.

Anemia, high ESR, and low A/G ratio in elderly patients should alert the clinician to investigate along the lines of multiple myeloma. Source

[!INFO] Blood picture in multiple myeloma:
MultipleMyelomaBloodPicture.png
Rouleaux formation - linear aggregates of RBCs.
(different from agglutination in which RBCs form grape like clusters)
A single plasma cells (arrow) is also seen.

Treatment of mulitple myeloma

  1. Induction of remissions
  2. Autologous stem cell transplantation
  3. Maintenance therapy after transplantation